MX2014006861A - Antimicrobial composition. - Google Patents

Antimicrobial composition.

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Publication number
MX2014006861A
MX2014006861A MX2014006861A MX2014006861A MX2014006861A MX 2014006861 A MX2014006861 A MX 2014006861A MX 2014006861 A MX2014006861 A MX 2014006861A MX 2014006861 A MX2014006861 A MX 2014006861A MX 2014006861 A MX2014006861 A MX 2014006861A
Authority
MX
Mexico
Prior art keywords
terpineol
isopropyl
weight
composition
antimicrobial
Prior art date
Application number
MX2014006861A
Other languages
Spanish (es)
Other versions
MX347389B (en
Inventor
Robert Joseph Cornmell
Megan Anne Diehl
Stephen Golding
John Robert Harp
Ian Peter Stott
Katherine Mary Thompson
Carol Lynn Truslow
Original Assignee
Unilever Nv
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Unilever Nv filed Critical Unilever Nv
Publication of MX2014006861A publication Critical patent/MX2014006861A/en
Publication of MX347389B publication Critical patent/MX347389B/en

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Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08Oxygen or sulfur directly attached to an aromatic ring system
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/04Oxygen or sulfur attached to an aliphatic side-chain of a carbocyclic ring system
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/06Oxygen or sulfur directly attached to a cycloaliphatic ring system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols

Abstract

The present invention relates to an antimicrobial composition and a method for disinfection involving the antimicrobial composition. It particularly relates to an antimicrobial composition for personal cleaning, oral care or hard surface cleaning applications. It was found that compositions comprising one or more isopropyl-methylphenols, terpineol and a carrier provide synergistic antimicrobial action. In a preferred aspect the composition also comprises 1 to 80 %-wt of one or more surfactants.

Description

ANTI MICROBIAL COMPOSITION Field of the invention The present invention relates to an antimicrobial composition and a method for disinfection involving the antimicrobial composition. It relates in particular to an antimicrobial composition for personal cleansing, oral care or hard surface cleaning applications.
BACKGROUND OF THE INVENTION Cleaning or soap compositions sanitizers and disinfectants are of great benefit to individuals, because proper use can generally reduce the number of germs and pathogens to which the individual is exposed. Thus, such compositions can play, for example, an important role in reducing the occurrence and spread of infectious diseases.
Sanitizing and disinfecting soap compositions comprising chlorine-based antimicrobial agent, such as triclosan, are known. Such compositions require a fairly long contact time to provide effective antimicrobial action. In practice, users, particularly children, do not spend much time cleaning and as a result cleaning with such compositions does not provide adequate prevention of superficial or typical infection or adequate protection against diseases. The user, in spite of cleaning his hands, in general will probably end up with removal relatively inadequate bacterial skin Therefore, it can cause contamination of additional animate and / or inanimate surfaces and contribute to the spreading of pathogens and consequent diseases. Users in general and children in particular, who wash contaminated hands before meals with slow-acting antimicrobial compositions for a relatively short time are at risk of contracting diseases.
Similarly, in the area of hard surface cleaning, for example, floor cleaning, table coverings or utensils, the antimicrobial in the compositions is in contact with the substrate for less than a few minutes, after which the surface It is either cleaned or rinsed with water. These short-time cleaning action scales are ineffective in providing the desired benefit, because most of the commonly known antimicrobials used in such products can take many minutes to hours to provide the desired death of microbes.
Therefore, there is a need to provide a composition which - upon application - provides relatively more effective antimicrobial action during a relatively short cleaning period, preferably about 30 seconds or less.
A well-established class of antimicrobially active compounds are phenolic compounds [P A Goddard and K A McCue in "Disinfection, Sterilization and Preservation", ed. S S Block, 5th edition, Lippincott, Williams and Wilkins, Philadelphia, 2001 pp. 255-282]. However, not everything Phenolic compound is suitable as an antimicrobial agent. Moreover, many phenols, even if they are antimicrobially active, can exhibit undesirable side effects, such as corrosivity, odor, and irritant or sensitizing effects when applied to human or animal skin.
A particularly well-known group of phenolic compounds are halogenated phenols. However, there are concerns about the use of chlorinated phenols as antimicrobials and herbicides, because they are perceived as contaminants, and are often associated with environmental toxicity, bioaccumulation and low biodegradability [JP Voets et al, J. Appl. Bact. Vol 40, p. 67-72 (1976); "Clorophenols in the terrestrial environment" (Chlorophenols in the terrestrial environment) J Jensen, Reviews of environmental contamination and toxicology (Revisions of environmental contamination and toxicology), vol 146 pp 25-51 (1996)].
WO 2010/046238 A1 discloses an effective antimicrobial composition, which provides rapid death of pathogenic bacteria and which comprises 0.01 to 5% by weight of thymol, 0.01 to 5% by weight of terpineol and a carrier. WO 2010/046238 A1 also describes a method for disinfecting a surface including the step of applying the above composition to the surface.
WO 1 1/17424 discloses viral inhibitory compositions for therapeutic use in vivo comprising a combination of (-) - carvone, geraniol and an additional essential oil component.
WO 04/035723 is directed to cleaning compositions and / or concentrated disinfection which bloom when diluted in water. Describes a concentrated hard surface cleaning composition comprising: a) from about 0.05 to about 10% by weight of a non-cationic antimicrobial agent; b) from about 1 to about 20% by weight of a water soluble organic solvent; c) from about 1 to about 20% by weight of an anionic soap surfactant; d) from about 1 to about 15% by weight of a hydrocarbon diluent; e) from about 0.001 to about 20% by weight of pine oil, which is at least 60% of terpene alcohols; f) optionally, from about 0 to about 10% by weight of optional materials selected from dyes, colorants, pH stabilizers and buffers, nonionic surfactants, fragrance / fragrance improvers, viscosity modifiers, insect repellents and light stabilizers; and g) the rest being water. Non-cationic antimicrobials based on phenols are preferred. Important constituents of pine oil include terpineol. A composition comprising 1.50% by weight of aromatic hydrocarbons (Aromatic 200), 1.00% by weight of Pine Oil 80, 1.50% by weight of PCMX (p-chloro-m-xyleneol), 2.00 is shown. % by weight of isopropyl alcohol, 20% by weight of NaCOS (sodium castor oil soap - 40%), 0.40% by weight of insect repellent, 73.60% by weight of water and added dye provides a reduction value of log 1 0 of more than 3 in a reduction suspension test microbial, after a contact time of 15 seconds, using 1: 60 to 1: 100 dilutions of the composition in water and one part of organism suspension. { Staphylococcus aureus or Salmonella choleraesuis).
FR 2 697 1 33 describes biocidal and / or biostatic compositions, comprising mono-oxygenated sesquiterpenes of the general formula Ci5HxO, wherein x is between 20 and 26 and aromatic compounds.
Despite the general availability of antimicrobial compounds and compositions, there remains a continuing need to find alternative antimicrobial compositions and active compounds that are suitable for use in such compositions. In particular, alternative compositions that provide fast antimicrobial action remain highly desirable in view of current consumer habits. Such alternatives can reduce dependence on current raw materials. Moreover, in the field of antimicrobials, the availability of alternatives may reduce the risk of developing resistance or microbial insensitivity to particular antimicrobial compounds.
In addition, there is a continuing need to reduce the total amount of active ingredients required in such an antimicrobial composition. This need can be driven, for example, by the desire for efficiency in terms of cost, because such compositions are particularly relevant for developing countries. Moreover, reducing the quantities can also be beneficial for environmental reasons.
A particular problem of certain antimicrobial actives, and especially some phenolic compounds, such as thymol, is that they are generally well perceptible due to their olfactory properties. Although the latter may be - at least for some species - appraised in certain fragrance compositions, they are considered too intense by some users when applied to effective concentrations for rapid disinfection. Additionally, a lower concentration of odoriferous compounds or the availability of antimicrobial compounds that are less or not at all odoriferous, allows greater flexibility to the manufacturer to provide alternative essences to its composition at lower doses. Hence, there is a need to provide alternative antimicrobial compositions and methods that require, preferably, lower concentrations and / or have a more acceptable sensory profile.
In view of the above-noted problems and disadvantages of the prior art, an object of the present invention is to provide alternative antimicrobial compositions.
A particular objective of the invention is to provide such compositions, requiring a lower dose of antimicrobial compounds.
Similarly, an object of the present invention is to provide an antimicrobial composition in which the olfactory contribution of the antimicrobially active compounds is reduced or in which the active compound contributes to providing an essence acceptable to the consumer or even appreciated by the consumer.
Another particular object of the invention is to provide an antimicrobial composition that contributes to reduce the contact time required in a method for disinfecting a surface.
In particular, an object of the invention is to provide an antimicrobial composition, which gives improved disinfection during cleaning of surfaces of the human body, such as the skin and the oral cavity.
Still another object of the present invention is to provide an alternative method for sanitizing and / or disinfecting, in particular of surfaces.
A further objective of the invention is to provide a method for disinfection with a reduced disinfection time. More specifically, an object of the invention is to provide a method, wherein the disinfection time of the method is less than 300 seconds, preferably less than 60 seconds, and more preferably less than 15 seconds.
In particular, an object of the invention is to provide a method for disinfection which gives improved disinfection during the cleaning of surfaces, in particular hard surfaces, or surfaces of the human body, such as the skin and the oral cavity.
BRIEF DESCRIPTION OF THE INVENTION We have now found that one or more of the above objects are fulfilled by the present invention. Thus, we have found that compositions comprising isopropyl-methylphenols Selected and terpineol provide synergistic antimicrobial action. Such compositions provide similar or more effective antimicrobial action at similar or lower concentrations when compared to thymol and alpha-terpineol. In particular, we have found that combinations of isopropyl methylphenols and terpineol according to this invention are capable of very rapid antimicrobial action. For example, we have found that complete microbial inactivation could be effected with compositions according to the present invention after a contact time of only 15 seconds. Moreover, the compositions according to the present invention are not based on the presence of halogenated phenols for their antimicrobial efficacy.
The isopropyl methylphenols of the present invention advantageously have an olfactory detection limit which is lower than that of other phenolic compounds, including thymol.
Accordingly, in a first aspect, the invention provides an antimicrobial composition comprising: i. 0.001 to 5% by weight of one or more isopropyl-methylphenols, ii. 0.001 to 5% by weight of terpineol, and iii. a carrier, wherein the one or more isopropyl-methylphenols have the following structure and where terpineol is selected from the group consisting of alpha-terpineol, beta-terpineol, gamma-terpineol, delta-terpineol, 4-terpineol and mixtures thereof.
According to a second aspect of the invention, there is provided a method for disinfecting a surface comprising the steps of to. applying a composition according to the invention to the surface; Y b. Remove the composition from the surface.
In a third aspect, the invention provides the use of a composition according to the invention for improved hygiene.
Detailed description of the invention So that there is no doubt, any characteristic of an aspect of the invention can be used in any other aspect of the invention. The word "undand" is meant to "include" but not necessarily "consist of" or "compose of". Thus, the term "undand" means that it is not limited to any of the elements subsequently declared, but optionally also includes unspecified elements of greater or lesser functional importance. In other words, the steps or options listed need not be exhaustive. Whenever the words "include" or "have" are used, these terms mean that they are equivalent to "understand" as defined above. It is noted that the examples given in the description below are intended to clarify the invention and are not intended to limit the invention to those examples per se.
Except in the examples, or where explicitly stated otherwise, all figures in this description that indicate material quantities or reaction conditions, physical properties of materials and / or use are to be understood as modified by the word "approximately." . Unless otherwise specified, the numerical ranges expressed in the format "from x to y" are understood because they include x and y. When, for a specific characteristic, they describe multiple preferred ranges in the "from x to y" format, it is understood that all the ranges that combine the different endpoints are also contemplated.
Phenol in its strictest sense refers to hydroxybenzene (CeHsO H), but where the word phenol is appropriate it can be referred to in its broadest meaning as understood by the skilled person, a member of the class of compounds which comprise at least one such characteristic hydroxybenzene moieties.
Throughout this description, the term disinfection refers to the reduction of the number of viable microorganisms in a given medium or on a given surface by physical or chemical means. Normally, disinfection involves the destruction or inactivation of said microorganisms. Both animate and inanimate media and surfaces are contemplated.
The term "microbicide" refers to a compound capable of killing, inhibiting the growth of or controlling the growth of microorganisms at a site; Microbicides include bactericides, fungicides and algaecides. The term "microorganism" includes, for example, fungi (such as yeast and mold), bacteria and algae.
The antimicrobial composition comprises one or more isopropyl methylphenols, terpineol and a carrier. Various components of the antimicrobial composition are described below.
The compositions of the present invention are preferred for non-therapeutic use, and more particularly preferred for use on cleaning surfaces of human body including skin, hair or oral cavity or for hard surface cleaning applications.
Selected Isopropyl Methylphenols The antimicrobial composition according to the invention comprises 0.001 to 5% by weight of one or more isopropyl-methylphenols. The composition preferably comprises 0.005 to 4.5% by weight, more preferably 0.01 to 4% by weight, still more preferably 0.02 to 3% by weight, even more preferably 0.03 to 2% by weight, still more preferably 0.04 to 1% by weight , still more preferably 0.05 to 0.75% by weight and still more preferably 0.1 to 0.5% by weight of the one or more isopropyl-methylphenols. In compositions that are intended to be diluted prior to application, the preferred minimum concentrations of one or more isopropyl-methylphenols may be greater. For example, when washing hands with water and a composition according to the invention, the foam produced is usually a 50% by weight dilution of the original composition. Similarly, in body wash situations, bars of soap or soap liquids are usually diluted to about 8% by weight of soap in water, corresponding to a dilution of about ten times of the product. Therefore, the compositions according to the invention which are intended to be diluted on use, preferably comprise 0.05 to 4.5% by weight, more preferably 0.1 to 4% by weight, even more preferably 0.2 to 3% by weight, even more preferably 0.4 to 1% by weight, and even more preferably 0.5 to 1% by weight of one or more isopropyl-methylphenols. Thus, the concentration of one or more isopropyl methylphenols in the antimicrobial composition is preferably such that, when the composition is diluted or dissolved with a suitable medium during use, the concentration in the diluted or dissolved mixture is still sufficient to be antimicrobial. effective.
The isopropyl methylphenol can be a simple compound or it can be a mixture of the isopropyl methylphenols as detailed below. In certain preferred embodiments, mixtures of isopropyl methylphenols are preferred, because such mixtures may show increased antimicrobial activity against a wider range of microbes. On the other hand, for reasons that include, for example, control over the formulation, it is preferred that in case the composition according to the invention comprises a mixture of such isopropyl methylphenols, the mixture preferably comprises at least 30%, more preferably at least 50%, still more preferably at least 70% and still more preferably at least 90% by weight of an isopropyl-methylphenols with respect to the total weight of the isopropyl-methylphenols.
At concentration ranges of isopropyl-methylphenols below the lower concentration limits of isopropyl-methylphenols, the desired fast-acting antimicrobial kinetics in combination with terpineol would not be met. At concentrations higher than the preferred higher concentrations of isopropyl-methylphenols, when in combination with a terpineol, as long as the action kinetics was not compromised, the present inventors have found that unlike in therapeutic / pesticide / herbicidal applications where the sensory aspects are not critical, in the present application, which is preferably an application of personal cleansing, oral care or cleaning of hard surfaces, the product is in contact with hands, mouth or other parts of the body, the sensory aspects including odor and skin sensation would be compromised.
One or more isopropyl-methylphenols have the following structure With respect to the hydroxy group, all positional isomers are contemplated according to the above structures. Examples of the isopropyl methylphenols selected according to the present invention are provided in Table 1.
Table 1 Preferably, the one or more isopropyl methylphenols are selected from 3-isopropyl-5-methylphenol and 4-isopropyl-3-methylphenol.
Advantageously, some compounds according to the invention have a weaker odor, when compared to that of thymol, or an odor which may be more appreciable to the consumer, when dosed in the compositions according to the invention at levels effective This benefit applies especially to, for example, 3-isopropyl-5-methylphenol and 4-isopropyl-3-methylphenol. The smell of 3-isopropyl-5-methylphenol, for example, is weaker, less tarry than thymol but still medicinal. 4-Isopropyl-3-methylphenol is practically odorless. Also for this reason, these compounds are preferred compounds.
Preferred isopropyl-methylphenol mixtures are also preferred.
Without wishing to be bound by theory, it is believed that the synergistic mode of antimicrobial action of the isopropyl methylphenols according to the present invention, in combination with terpineol is similar for the different isopropyl methylphenols.
The degree to which the isopropyl methylphenols according to the present invention are soluble in water or in organic solvents can be adequately expressed by the logarithm of the partition coefficient of octanol / water, log. { P.}. . This partition coefficient is a measure for the distribution of a solute between water and octanol in equilibrium. The value of the partition coefficient can also be predicted using computational methods. A commonly used predicted value is the so-called AlogP value. A preferred definition and calculation method of AlogP values is provided in A. K. Ghose, V. N. Viswanadhan, and J .J. Wendoloski, J. Phys. Chem. A, vol 102, p. 3762 (1998). Due to the standardized calculation as described by Ghose et al, the AlogP values of different compounds can be compared with each other and used to assess the similarity of or difference between different compounds. For example, phenol has a AlogP value of 1.59 and the thymol has an AlogP value of 3.27. Such a comparison can also be extended to other properties that are thought to refer to the same molecular properties that underlie the value of AlogP. Although it is not desired to link to a theory in this respect, it is believed that there is a correlation between Alog P and the antimicrobial efficacy of the isopropyl-methylphenols according to the present invention. Therefore, the isopropyl methylphenols according to the present invention preferably have an AlogP value of between 2.0 and 4.5, more preferably between 2.2 and 4.4, still more preferably between 2.4 and 4.1, and even more preferably between 2.5 and 4.0.
Suitable isopropyl methylphenols according to the present invention may be of commercial origin or obtained via synthetic chemical methods. Such methods are generally well known to the person skilled in the art.
Terpineol The antimicrobial composition according to the invention comprises 0.001 to 5% by weight of terpineol. The composition preferably comprises 0.005 to 4.5% by weight, more preferably 0.01 to 4% by weight, even more preferably 0.02 to 3% by weight, still more preferably 0.03 to 2% by weight, still more preferably 0.04 to 1% by weight. weight, still more preferably 0.05 to 0.75% by weight and even more preferably 0.1 to 0.5% by weight of terpineol. In compositions intended to be diluted before application, the minimum preferred concentrations of terpineol may be higher, for the same reasons as regards isopropyl-methylphenols. Therefore, the compositions according to the invention intended for dilution on use comprise, preferably 0.05 to 4.5% by weight, more preferably 0.1 to 4% by weight, even more preferably 0.2 to 3% by weight, still more preferably 0.4. to 1% by weight, and even more preferably 0.5 to 1% by weight of terpineol. Any of these concentration ranges for terpineol is preferably combined with any of the concentration ranges for the one or more isopropyl-methylphenols specified above. Therefore, the antimicrobial composition according to the invention comprises, for example: a. 0.05 to 0.4% by weight of one or more isopropyl-methylphenols; and b. 0.05 to 1% by weight of terpineol.
The terpineol may be a simple compound or it may be a mixture of the terpineol isomers as detailed below. Mixtures of terpineols are preferred, because such mixtures may show increased antimicrobial activity against a wider range of microbes. In case the composition according to the invention comprises such a mixture of terpineols, the mixture preferably comprises at least 30%, more preferably at least 50%, still more preferably at least 70% and still more preferably at least 90% in weight of an isomer of terpineol with respect to the total weight of terpineol. Preferably, said isomer of terpineol is alpha-terpineol. The preferred concentration ranges of terpineol are important for the same reasons as the preferred concentration ranges of one or more isopropyl methylphenols for comply with the desired fast action antimicrobial kinetics, while not being sensuously unpleasant when used in products for personal cleansing, oral care or hard surface cleaning applications.
Isomers of terpineol Terpineol exists as different isomers, which are all considered terpineols. Terpineol is selected from the group consisting of alpha-terpineol, beta-terpineol, gamma-terpineol, delta-terpineol, 4-terpineol, and mixtures thereof. More preferably, terpineol is selected from the group consisting of alpha-terpineol, beta-terpineol, gamma-terpineol, detla-terpineol and mixtures thereof. By nature, the isomeric compounds alpha-terpineol, beta-terpineol and gamma-terpineol are among the most abundant terpineols and often occur together in mixtures. Therefore, even more preferably, terpineol is selected from the group consisting of alpha-terpineol, beta-terpineol, gamma-terpineol and mixtures thereof. The structures of these isomers are shown schematically in Table 2 below.
Table 2 Where applicable, the different stereoisomers of these terpineol isomers are contemplated. For example, cis-beta-terpineol and trans-beta-terpineol are both contemplated. Thus, compositions comprising enantiomerically pure radicals, racemic mixtures and / or mixtures of different stereoisomers are also preferable.
These terpineols are all members of the mentenol class of compounds [AL Gunatilaka, Natural Products in Plants: Chemical Diversity in the Wiley Encyclopedia of Chemical Bioology, pp. 1-17 and E Breitmaier, Terpenes: flavors, fragrances, phamaca, pheromones (Terpenes: flavors, fragrances, drug, pheromones); p. 17, Wiley-VCH, 2006], also called oxytetrahydrocimenes [F Heusler, The Chemistry of the Terpenes, trans. F J Pond, P Blakistons's are & Co, FMadelfia, 1 902, p. 21], which can be defined as monohydroxyl alcohol derivatives of p-mentene, with the generic formula C10H 17OH. Combinations of these terpineol isomers are frequently found together in nature, because it is generally believed that their biosynthesis proceeds via closely related synthetic routes. Without wishing to be bound by theory, it is believed that the antimicrobial mode of action of these isomers of terpineol in combination with the isopropyl methylphenols according to the present is similar.
Terpineoies can also be referred to by alternative names as detailed below in Table 3.
Table 3 Terpineol can be added to the antimicrobial composition in purified form. Alternatively, pine oil comprising terpineol can be added to the antimicrobial composition while ensuring that terpineol is present at the desired concentration in the composition of the present invention.
Carrier The antimicrobial composition according to the invention comprises a carrier. The carrier is preferably selected from the group consisting of water, oil, solvent, inorganic particulate material, starch, air and mixtures thereof. The carrier is preferably from 0.1 to 99% by weight of the composition. The antimicrobial composition can be in the form of a solid, liquid, gel, paste or soft solid and the carrier can be selected by a person skilled in the art depending on the format of the antimicrobial composition.
Examples of inorganic particulate materials include clay, talc, calcite, dolomite, silica, and aluminosilicate. Examples of oils include mineral oils, oils of biological origin (e.g., vegetable oils) and oils derived from petroleum and waxes. The oils of biological origin are preferably based on triglyceride. Preferably, the carrier oil is not a perfume oil. Thus, the carrier oil preferably does not contribute substantially to the odor of the composition, more preferably does not contribute to the odor of the composition, more preferably, does not contribute to that odor. Examples of solvents include alcohols, ethers and acetone. The starch can be natural starch obtained from food grains or can be a modified starch.
In certain preferred embodiments, suitable solvents include, for example, water; glycols, including ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol, and polypropylene glycol; glycol ethers; alcohols, such as methanol, ethanol, propanol, phenethyl alcohol and phenoxypropanol; ketones, including acetone and methyl ethyl ketone; esters, including ethyl acetate, butyl acetate, triacetyl citrate and glycerol triacetate; carbonates, including propylene carbonate and dimethyl carbonate; and mixtures thereof. It is preferred that the solvent be selected from water, glycols, glycol ethers, esters and mixtures thereof. In certain preferred embodiments, suitable solid carriers include, for example, cyclodextrin, silicas, diatomaceous earth, waxes, cellulosic materials, alkali and alkaline earth metal salts (eg, sodium, magnesium, potassium (eg, chloride, nitrate, bromide, sulfate) and carbon.
The air can be used, for example, as a carrier when the isopropyl methylphenols according to the invention and / or the terpineol are atomized or otherwise dispersed as a fine mist.
Particularly preferred carriers are water or oil / solvent and a carrier that is a mixture of water and oil is even more preferred. Thus, in many intended applications such as personal care / washing, oral care and hard surface cleaning, the antimicrobial composition can be formulated with either an aqueous base or an oil / solvent base. The compositions with an aqueous base (water being the carrier), can also be, for example, products in gel format. The compositions with an oil / solvent base can be, for example, products in the form of anhydrous stick or products containing propellants.
Thus, the antimicrobial composition can be, for example, preferably an antimicrobial composition for personal care of anhydrous stick in an oil / solvent base, wherein the composition has a water content of less than 0.01% by weight, and wherein the composition is preferably free of water. Alternatively, the antimicrobial composition can be, for example, preferably a propellant-driven antimicrobial personal care composition, also comprising a propellant. The air can also be used as a propellant, for example, in the form of compressed or liquefied air.
However, the most preferred product format has an emulsion base (water and / or oil being the carrier) or is capable of forming an emulsion upon dilution, eg, soap products in liquid, solid, lotion or semi-solid form for hand washing, face side, body washing or shaving applications; toothpastes / toothpastes for oral care applications or products for cleaning hard surfaces in bar or liquid forms. If the product comprises an emulsion base, it also preferably comprises one or more surfactants as described below.
Surfactants The antimicrobial composition according to the invention preferably comprises from 1 to 80% by weight of one or more surfactants. The surfactants may, for example, advantageously contribute to cleaning efficiency or formulation stability of a composition.
Thus, the antimicrobial composition according to the invention comprises preferably to. 0.001 to 5% by weight of the one or more isopropyl methylphenols according to the invention, b. 0.001 to 5% by weight of terpineol, c. a carrier, and from 1 to 80% by weight of one or more surfactants.
It is particularly preferred that the antimicrobial composition comprises from 1 to 80% by weight of one or more surfactants in combination with the one or more isopropyl methylphenols, and terpineol at its most preferred concentrations as specified above.
In general, surfactants can be chosen from the surfactants described in textbooks well known as "Surface Active Agents" (active surface agents) vol. 1, by Schwartz & Perry, Interscience 1 949, vol. 2 by Schwartz, Perry & Berch, Interscience 1958, and / or the current edition of "McCutcheon's Emulsifiers and Detergents" published by Manufacturing Confectioners Company or in "Tenside-Taschenbuch", H. Stache, 2nd ed. , Cari Hauser Verlag, 1981; "Handbook of Industrial Surfactants" (4th ed.,) By Michael Ash and I rene Ash; Synapse I nformation Resources, 2008. Any type of surfactant, is anionic, cationic, non-ionic, zwitterionic or amphoteric can be used. Preferably, the one or more surfactants are anionic, non-ionic, or a combination of anionic and nonionic surfactants. More preferably, the one or more surfactants are anionic.
A particularly preferred surfactant is soap. The soap is a suitable surfactant for personal washing applications of the antimicrobial composition of the invention. The soap is preferably C8-C24 soap, more preferably a C10-C20 soap and most preferably C12-C16 soap. The soap may or may not have one or more double bonds or triple carbon-carbon bonds. The cation of the soap can be, for example, an alkali metal, alkaline earth metal or ammonium. Preferably, the soap cation is selected from sodium, potassium or ammonium. More preferably, the cation of the soap is sodium or potassium.
The soap can be obtained by saponifying a fat and / or a fatty acid. Fats or oils may be fats or oils generally used in the manufacture of soap, such as tallow, tallow tallow, palm oil, palm stearin, soybean oil, fish oil, castor oil, rice bran oil , sunflower oil, coconut oil, babassu oil, palm kernel oil and others. In the above processes, the fatty acids are derived from oils / fats selected from coconut, rice bran, walnut, tallow, palm, palm kernel, cottonseed, soybean, castor, etc. The fatty acid soaps can also be prepared synthetically (for example, by the oxidation of petroleum or by hydrogenation of carbon monoxide by the Fischer-Tropsch process). Resin acids, such as those present in pulp oil, can be used. Naphthenic acids are also suitable.
The tallow fatty acids can be derived from several animal sources. Other similar mixtures, such as those of palm oil and those derived from various animal and lard seals are also included.
A typical fatty acid mixture consists of 5 to 30% by weight of coconut fatty acids and 70 to 95% by weight of fatty acids eg hardened rice bran oil. Fatty acids derived from other suitable oils / fats, such as walnut, soy, tallow, palm, palm kernel, etc., may also be used in other desired proportions. The soap, when present in solid forms of the present invention, is preferably present in an amount of 30 to 80%, more preferably 50 to 80%, and even more preferably 55 to 75% by weight of the composition. The soap, when present in liquid forms of the composition, is preferably present in 0.5 to 20%, more preferably 1 to 10% by weight of the composition.
Other preferred surfactants are glycipates of fatty acids and fatty amphocarboxylates. These surfactants are particularly preferred in skin and hair cleansing compositions, due to their mild detergency and highly foaming nature. Glycinates of fatty acids are salts of amides of glycine fatty acids, including, for example, sodium cocoyl glycinate. The fatty amphocarboxylates are amphoteric surfactants including, for example, sodium lauroamphoacetate (i.e., 2- [1- (2-hydroxyethyl) -2-undecyl-4,5- sodium dihydroimidazol-1 -io-1-yl-acetate). Still another example of suitable surfactants are derivatives of isethionates, including acyl isethionates.
The antimicrobial composition of the invention is also useful in hard surface cleaning applications. In such applications, the preferred surfactants are nonionic surfactants, such as C8-C22, preferably Ce-C6 fatty alcohol ethoxylates, comprising between 1 and 8 ethylene oxide groups, when the product is in the form liquid When the product for hard surface cleaning applications is in the solid form, the surfactants are preferably selected from non-ionic surfactants of primary alkyl sulfates, secondary alkyl sulfonates, alkyl benzene sulfonates, ethoxylated alkyl sulphates or alcohol ethoxylate. The composition may further comprise an anionic surfactant, such as alkyl ether sulfate, preferably those having between 1 and 3 ethylene oxide groups, either of natural or synthetic source and / or sulfonic acid. Sodium lauryl ether sulfates are especially preferred. The alkyl polyglucoside may also be present in the composition, preferably having a carbon chain length between C6 and C16. Other classes of useful surfactants include cationic surfactants, such as long chain quaternary ammonium compounds and amphoteric surfactants, such as betaines and alkyl dimethyl amine oxides. Concentrations of suitable surfactants in liquid forms of hard surface cleaning application are generally from about 0.5 to 10%, preferably from 1 to 5% by weight of the composition. In solid compositions, the surfactant is preferably present in 5 to 40%, preferably 1 to 30% by weight of the composition.
The antimicrobial composition of the invention is useful in compositions for oral care, for example, in a toothpaste / toothpaste or an oral rinse product. In such applications, preferred surfactants are anionic, nonionic or amphoteric, preferably anionic or amphoteric in nature. The anionic surfactant is preferably an alkali metal alkyl sulfate, more preferably a sodium lauryl sulfate (SLS). Mixtures of anionic surfactants can also be used. The amphoteric surfactant is preferably a betaine, more preferably an alkylamidopropyl betaine (wherein the alkyl group is a linear C 1 0 -C 8 chain), and most preferably is cocoamidopropyl betaine (CAPB). Mixtures of amphoteric surfactants can also be used. Suitable surfactant concentrations in oral care application are generally from about 2% to about 15%, preferably from about 2.2% to about 10%, more preferably from about 2.5 to about 5% by weight of the total composition.
Thus, it is highly preferred that the antimicrobial compositions include soap, alkyl sulfate or linear alkyl benzene sulfonate as the surfactants. More preferably, the one or more surfactants are selected from the group consisting of soaps, alkyl sulfates and linear alkyl benzene sulphonates.
Liquid and solid compositions The antimicrobial composition can be in the form of a solid, a liquid, a gel or a paste. A person skilled in the art can prepare compositions in various formats by choosing one or more carrier materials and / or surfactant. The antimicrobial compositions of the present invention are useful for cleaning and care, in particular skin cleansing and skin care. It is envisioned that the antimicrobial composition can be used as a leaving product or a wash product, preferably a wash product. The antimicrobial composition of the present invention can also be used for cleaning or care of hard surfaces, such as glass, metal, plastic and the like.
A particularly preferred carrier is water. When the water is present, it is preferably present in at least 1%, more preferably at least 2%, still more preferably at least 5% by weight of the composition. When water is the carrier, both liquid and solid compositions are possible. Different amounts of water may be preferred depending on the product format. When the water is the carrier, a preferred liquid antimicrobial composition according to the invention comprises: to. 0.01 to 5% by weight of one or more isopropyl-methylphenols, b. 0.05 to 5% by weight of terpineol, c. 10 to 99.9% by weight of water, and, d. 1 to 30% by weight of surfactant.
The liquid antimicrobial composition is useful for skin cleansing, in particular for hand washing or a face wash.
When the water is the carrier, an antimicrobial composition according to the invention comprises: to. 0.05 to 5% by weight of one or more isopropyl-methylphenols, b. 0.05 to 5% by weight of terpineol, c. 5 to 30% by weight of water, and d. 30 to 80% by weight of surfactant.
The solid antimicrobial composition is preferably in the form of a solid formed, more preferably a rod. The solid antimicrobial composition is particularly useful for cleaning the skin in particular for hand washing or a face wash.
Such a solid bar-shaped antimicrobial composition can be, for example, a bar of soap. The soap bar compositions are well known and can be similar to the following non-limiting example composition, comprising 75.6% by weight of anhydrous sodium soap, 1.0% by weight of glycerin, 0.5% by weight of sodium carbonate, 0.2% by weight of EHDP (ethane-1-hydroxy-1, 1-disphosphonate) acid , 0.04% by weight of EDTA salt (ethylenediaminetetraacetic acid), 8.5% by weight of magnesium silicate hydrate (talcum), 0.7% by weight of sodium chloride, 0.05% by weight of dyes, 0.75% by weight of perfume, 0.05 to 10% by weight of antimicrobial agents including isopropyl methylphenols and terpineol according to the present invention, and water up to 100% by weight.
Alternatively, the inorganic particulate material is also a suitable carrier. When the inorganic particulate material is the carrier, the antimicrobial composition is in a solid form. Preferably, the inorganic particulate material is talc. When the inorganic particulate material is talcum, the solid antimicrobial composition is particularly useful as a talcum powder for face or body application.
According to another embodiment, a solvent other than water is a preferred carrier. Although any solvent can be used, alcohol is a preferred solvent. Short chain alcohols - in particular, ethanol, propanol and isopropanol - are particularly preferred as a carrier for an antimicrobial hand sanitizer composition or an antimicrobial cleaner.
Solvents such as ethanol and isopropanol generally show antimicrobial efficacy themselves. However, they are also volatile and can easily evaporate during application of the composition. Thus, their levels on the surface being treated could even be reduced until below the minimum level required for antimicrobial action, before the minimum period necessary for disinfection has passed. In contrast, terpineol and isopropyl methylphenols according to the present invention are much less volatile and therefore can produce a prolonged antimicrobial action after being applied to the skin.
Additional ingredients The composition may further comprise several additional ingredients known to a person skilled in the art. Such additional ingredients include, but are not limited to, perfumes, pigments, preservatives, emollients, sunscreens, emulsifiers, gelling agents, thickening agents, humectants (e.g., glycerin, sorbitol), sequestrants (e.g., EDTA) or polymers ( for example, cellulose derivatives to structure such methyl cellulose).
Both terpineol and some of the isopropyl methylphenols according to the invention can contribute to the olfactory properties of the composition. Although some of these compounds could be applied for example in perfume compositions, the present invention is directed towards antimicrobial compositions. Therefore, the composition is preferably not a perfume composition, although other perfume components may be present. Here, a perfume composition is defined as a composition comprising a plurality of olfactory components, wherein the composition is intended solely to provide a harmonious essence.
Synergistic effect of the invention The inventors have surprisingly found that while one or more of the isopropyl methylphenols according to the present invention alone or terpineol alone does not individually provide the rapid antimicrobial kinetic action, a combination of one or more isopropyl-methylphenols and terpineol at selective concentrations provides an antimicrobial action, which is especially important in a washing process, where the contact time of the antimicrobial actives with the surface is low, that is, of the order less than 5 minutes, preferably less than 2 minutes, more preferably less than one minute and in many cases less than 1.5 seconds.
Synergistic combinations of isopropyl-methylphenols and terpineol The antimicrobial action of two or more active compounds is considered additive if the combined action merely results from the addition of the effects that the individual components would have in isolation. In contrast, the antimicrobial action of two or more active compounds is considered synergistic if the combined effect of the two or more compounds is stronger than expected based on the presumption of additivity. Without wishing to link to a theory, it is believed that the antimicrobial action of a compound is improved by the action of the other compound and vice versa. Such improvement may originate, for example, from cooperative interaction between the mechanisms of antimicrobial action at the molecular level. Such antimicrobial action may manifest itself, for example, by the fact that lower concentrations of active compounds are required to obtain complete microbial death, or alternatively that the same degree of microbial death is achieved in a shorter time.
If an antimicrobial composition comprising two or more Active compounds capable of synergistic antimicrobial action can be determined, for example, by following the procedures and using the criteria as outlined in Example 1 below. Normally, evidence of synergistic antimicrobial action is provided at concentrations below the minimum biocidal concentrations of each of the components when taken individually. However, it is generally believed that the synergistic action can still occur when the concentration of one or more of the active compounds is high above their minimum biocidal concentration (when taken individually).
The antimicrobial composition according to the present invention preferably comprises one or more isopropyl-methylphenols and terpineol according to the invention at concentrations to which they are capable of synergistic antimicrobial action. Thus, the concentrations of one or more isopropyl methylphenols and terpineol in the antimicrobial composition are preferably such that, when the composition is diluted or dissolved with a suitable medium during use, (eg, when washing hands with water and a composition according to the invention) the concentration in the diluted or dissolved mixture is still sufficient to be antimicrobially effective. That is, in order to be capable of synergistic antimicrobial action, the concentrations of the one or more isopropyl-methylphenols and the terpineol in the composition (Ccomp, phenoxy, and CComp, terp, respectively) are preferably such that upon application, at a concentration given one or more isopropyl-methylphenols in the application medium (Cmed, phenol), terpineol is available at at least a minimum medium concentration (Cmed, terp) or vice versa (ie, so that at a Cmed, given terp, a Cmed, minimum phenol is available, sufficient to provide synergistic antimicrobial action ). Here, the means of application denotes the medium in which the antimicrobial action desirably takes place. For example, in personal care applications such as hand washing, the composition may be a solid soap bar. In that CaSO, Ccomp refers to the concentration of the component in the bar of soap, while C med refers to the concentration in the foam. The minimum and optimum concentrations can be determined, for example, by a protocol as described for Example 1 or by one of the standards as detailed below. It is generally preferred that the concentrations of one or more isopropyl methylphenols and terpineol in the composition according to the invention are equal to or greater than the optimum concentrations in the application medium, because in many typical applications, the composition is already either used pure or diluted to form the application medium.
Surprisingly, the synergy between isopropyl-methylphenols and terpineol in compositions according to the invention occurs over a wide range of concentrations and concentration ratios. Depending on the factors including the type of antimicrobial composition, its intended application (for example, a hard surface cleaner, a skin cleanser or a hand sanitizer) different ranges of concentration and proportions will be preferred.
Thus, when for example, an antimicrobial action against E. coli is desired, the data of Example 1 can be used to determine preferred average Cmd concentrations. For example, in case where complete microbial inactivation is desired in the particular medium of Example 1 and if the isopropyl-methylphenols are 2-tert-butylphenol, and C med, phenol is selected as 0.025% (w / v), Cmed. Terp is preferably at least 0.15% (p / v) and vice versa.
Alternatively, the desired antimicrobial effect can be obtained by selecting a proportion of the respective concentrations of the one or more isopropyl-methylphenols and terpineol. In view of the considerations described above with respect to the intended antimicrobial efficacy and other considerations, including for example, sensory properties, solubility, economic considerations, a concentration ratio of isopropyl-methylphenols to terpineol greater than one is preferred in some applications, while a concentration ratio of isopropyl-methylphenols to terpineol is smaller than one is preferred in others, whereby the concentrations are expressed in% by weight.
Thus, in case where a ratio of concentration of isopropyl-methylphenols to terpineol smaller than one is desired, then the antimicrobial composition according to the invention preferably comprises one or more isopropyl-methylphenols and terpineol in a concentration ratio ( isopropyl-methylphenols: isopropyl-methylphenols) between 1: 2 and 1: 1 2, where the concentration is expressed as percent in weight.
Alternatively, in case where a concentration ratio of isopropyl-methylphenols to terpineol greater than one is desired, then the antimicrobial composition according to the invention preferably comprises one or more isopropyl-methylphenols and terpineol in an applicable concentration ratio as it is specified later in the present.
In a preferred embodiment of the invention, the synergistic antimicrobial composition comprises 3-isopropyl-5-methylphenol and 2- (4-methyl-1-cyclohex-3-enyl) propan-2-ol. Preferably, a weight ratio of 3-isopropyl-5-methylphenol to 2- (4-methyl-1-cyclohex-3-enyl) propan-2-ol is from 1/6/06 to 1/51, preferably from 1 / 006 to 1 / .0.19 or 1 / .03 to 1/1 .5, preferably 1 / .33 to 1 / .5.
A further advantage of the present invention is that it is observed that the treatment of a surface with a composition according to the invention comprising one or more isopropyl-methylphenols and terpineol, surprisingly allows continued protection of the surface against the growth of microbes over a period of time. substantial later.
Effect of including surfactant Favorably, suitable compositions in washing processes as described above include a surfactant for the cleaning action. To the further surprise of the inventors, although the surfactant alone does not provide rapid antimicrobial death to the concentration present in washing processes, provides further improvement in the degree of reduction in viable microbial beads on the surface in the short period when the surfaces are washed with a composition comprising one or more isopropyl methylphenols, terpineol and additionally surfactant. Thus, although the surfactant is generally known to be responsible for washing soil and also antimicrobial actives used in the composition, in the present invention, it provides a highly useful additional benefit since it improves the reduction of viable microbial counts in a composition comprising a combination of isopropyl-methylphenols and terpineol alone.
However, it was surprisingly found that certain surfactants can reduce the activity of antimicrobial agents according to the invention. This happens for example, with cocoyl glycinate and lauroanfoacetate. In general, surfactants are required in cleaning compositions to obtain good cleaning results. Because inter alia it is an object of this invention to provide antimicrobial cleansing compositions, therefore it is also an object of this invention to provide isopropyl methylphenols capable of improved antimicrobial action upon combination with terpineol in the presence of such surfactants. It was found that in particular 3-isopropyl-5-methylphenol and 4-isopropyl-3-methylphenol show improved antimicrobial action in combination with terpineol. Therefore, the composition according to the invention preferably comprises one or more isopropyl-methylphenols selected from the group consisting of 3- Sodpropyl-5-methylphenol and 4-isopropyl-3-methylphenol. More specifically, it is preferred that in the case of the composition according to the invention comprise a surfactant selected from cocoyl glycinate and lauroanmphoacetate, that the isopropyl-methyphenol is selected from the group consisting of 3-isopropyl-5-methylphenol and 4-isopropyl. -3-methylphenol.
Method according to the invention According to the second aspect, the invention relates to a method for disinfecting a surface comprising the steps of to. applying a composition according to the invention on the surface; Y b. Remove the composition from the surface.
Preferably, the surface is skin. Thus, for example, a surface such as the hands, face, body or oral cavity is contacted with the composition of the invention. If the surface is a surface of a human or animal body, the preferred method is a non-therapeutic method to disinfect a surface. Alternatively, the surface is any hard surface. Typically, such hand surfaces are surfaces that commonly require cleaning and preferably also require sanitization or disinfection. Such surfaces can be found in many home or industrial environments, and may include, for example, kitchen and bathroom surfaces, table tops, floors, walls, windows, utensils, cutlery and crockery. Such surfaces can be made from many different materials, including for example, plastic, wood, metal, ceramic, glass, concrete, marble and painted surfaces.
The composition can be applied to the surface by any suitable means known to the skilled person. For example, a suitable means may be to empty, drip, atomize or clean in the case of liquid compositions.
Preferably, the method includes diluting or dissolving the composition with a suitable solvent, preferably water, before or while applying the composition to the surface. Such a solution is particularly preferred in case the composition is a solid composition. Alternatively, the solid compositions may also be directly spread, rubbed or sprayed, for example, in the form of a powder.
The method according to the first aspect of the present invention also includes the step of removing the composition from the surface. Here, removing the composition also involves partially removing the composition, because traces of the composition may remain on the surface. In many typical situations, such as skin washing or hard surface cleaning, it is acceptable or sometimes even desirable if part of the composition - in particular certain active ingredients - remains on the surface. Therefore, step b preferably involves removing at least 5%, more preferably at least 10%, even more preferably at least 25%, still more preferably at least 50% and still more preferably at least 75% of the composition in weigh. Preferably, the step of removing the composition comprises rinsing the surface with a suitable solvent or cleaning the surface with a suitable cleanser, more preferably, this step consists of rinsing the surface with a suitable solvent or cleaning the surface with a suitable wipe. Alternatively, the removal step may also include evaporation of part of the composition, for example, when the composition comprises volatile components, for example solvents.
A suitable means for rinsing the surface is water, but it could also be, for example, a mixture of water and alcohol. It was then rinsed preferably with sufficient amounts of water after a predetermined period to remove any visible or sensory residue from the composition. Alternatively, an alcohol wipe or wipe impregnated with water / alcohol can be used to clean the surface to be visibly free of the antimicrobial composition. The step of removing the composition (for example, by rinsing or cleaning the surface) is preferably initiated less than 5 minutes, more preferably less than 2 minutes, even more preferably less than 1 minute, still more preferably less than 30 seconds and still more preferably less than 20 seconds after the start of the step of applying the composition on the surface, due to the surprisingly rapid antimicrobial action of the compositions according to the present invention. Even though the partial microbial death may be almost instantaneous upon application of the composition according to the invention, it is preferred that the step of removing the composition from the surface starts at least 5 seconds, preferably at least 10 minutes. seconds, more preferably at least 15 seconds after the beginning of the step of applying the composition on the surface, in order to effect the optimal antimicrobial action. The combinations of these times in time intervals are also preferred. Therefore, it is particularly preferred that the step of removing the composition from the surface (ie, step b) starts between 2 minutes and 5 seconds, more preferably between 1 minute and 10 seconds, even more preferably between 30 and 10 seconds and still more preferably between 20 and 15 seconds after the start of the step of applying the composition on the surface (ie, step a).
Disinfection time These times between applying the composition and rinsing or cleaning are preferably related to the time of disinfection, in order to ensure optimal cleaning and sanitization of the surface. Therefore, the preferred invention relates to a method, wherein the disinfection time T of said method is less than 300 seconds, preferably less than 60 seconds, and more preferably less than 15 seconds; wherein T is defined as the time that elapses from the time of adding the composition to a microbial culture until the number of microbes per unit volume of the culture is reduced by a factor of 100 000; and wherein the initial number of microbes preferably exceeds approximately 100,000,000 microbes per milliliter and wherein the composition is preferably a liquid composition.
The disinfecting action of the method (as can be expressed in terms of the disinfection time T) is determined preferably in accordance with the protocol of Example 1 as described hereinafter. This test refers to a standardized test environment, in which the microbial culture is kept in suspension. A suitable test in a similar way is the standard suspension method described in the European Standard EN 1276, with the proviso that the disinfection time is adapted to fit the above criteria as will be clear to a person skilled in the art. Alternatively, one of the test methods as described in WO 2010/046238 may be applied, for example, to establish the disinfection action.
Such test methods may also be used preferably by the skilled person to determine the optimum concentrations of one or more isopropyl methylphenols and terpineol in an antimicrobial composition according to the present invention.
Alternatively, because the method is directed towards surface disinfection, the disinfection time can also be determined by test methods involving a surface. Therefore, the invention preferably relates to a method according to the present invention, wherein the surface disinfection time T2 of said method is less than 60 seconds, preferably less than 15 seconds, where T2 is defined as the time that starts from the moment of applying the composition to the surface to be disinfected, after which the number of microbes per unit area is reduced by a factor of 1 0000 (ie, a logarithmic reduction 4), wherein the initial number of microbes preferably exceeds 103, more preferably 1 05, and even more preferably 10 7 microbes per square centimeter. Such tests may be performed, for example, as described in WO 2010/046238, or as described in the European Standards EN 13697: 2001 and EN 1500: 1997.
Use according to the invention The invention preferably provides non-therapeutic benefits. Thus, for example, the invention relates to the use of an antimicrobial composition according to the present invention for faster reduction in the viable microbial count.
Thus, according to the third aspect of the invention, the use of a composition according to the invention for improved hygiene is provided. Such use refers, for example, to the use of an antimicrobial composition comprising the one or more isopropyl-methylphenols, terpineol and a carrier, for reduction in the viable microbial count, preferably rapid reduction of viable microbial count. In this way, such use is preferably the use in a method for disinfection. The rapid reduction in the viable microbial count is therefore preferably referred to the use for disinfection whereby the disinfection time is less than 300 seconds, preferably less than 60 seconds, and more preferably less than 15 seconds. Thus, disinfection is preferably defined similar to the disinfection times T and T2 as described above.
In this way, the use of a composition according to the invention for improved hygiene of surfaces of the human body is provided. Such surfaces include, for example, skin, hands and the oral cavity. According to a preferred aspect, the invention relates to the use of a composition according to the invention for improved hand hygiene. According to another preferred aspect, the invention relates to the use of a composition according to the invention for improved oral hygiene.
The microbicidal compositions of the present invention can be used to inhibit the growth of microorganisms by introducing a microbicidally effective amount of the compositions, on, into or at a site subject to attack. For example, in the field of institutional and industrial applications, suitable locations include, for example: industrial process water including electro-coating deposition systems, cooling towers and air scrubbers; gas scrubbers; wastewater treatment; ornamental fountains; reverse osmosis filtration; ultrafiltration; ballast water; evaporative condensers and heat exchangers; pulp and paper process fluids and additives; mineral pastes; starch; plastic; emulsions; dispersions; paintings; latex; coatings, such as varnishes; construction products, such as mastics, mastics and senators; construction adhesives, such as ceramic adhesives, carpet backing adhesives and laminating adhesives; industrial or consumer adhesives; photographic chemicals; printing fluids; home and institutional products used in restaurants, health care facilities, schools, food processing facilities and farms including, cleaners, sanitizers and disinfectants, wipes, soaps, detergents, floor polishes and laundry rinse water; cosmetics; toiletries; shampoos; working fluids in metals; conveyor lubricants; hydraulic fluids; skin and skin processing products; textiles; textiles and textile processing products; wood and wood processing products, such as plywood, chipboard, laminated wood, flakeboard, laminated beams, oriented fiberboard, hardboard and particle board; oil and gas processing fluids, such as injection fluids, fracture fluids, drilling mud and produced water; fuel transportation and storage systems; conservation of agricultural auxiliaries; preservation of surfactants; medical devices; conservation of diagnostic reagents; food preservation, such as wrapping paper or plastic foods; food, beverages and industrial process pasteurizers; toilet bowls; recreational water; pools; and spas.
Preferably, the microbicidal compositions of the present invention are used to inhibit the growth of microorganisms at a site selected from one or more of the mineral pastes, pulp and paper processing fluids and additives, starch, emulsions, dispersions, paints, latexes , coatings, construction adhesives (such as ceramic adhesives), carpet backing adhesives, photographic chemicals, printing fluids, home and institutional products, such as cleaners, sanitizers, disinfectants, wipes, cosmetics, toiletries, shampoos, soaps, detergents, floor polishes , laundry rinse water, working fluids in metals, textile products, wood and wood products, conservation of agricultural auxiliaries, preservation of surfactants, conservation of diagnostic reagents, food preservation, industrial process pasteurizers, beverages, food and fluids of oil and gas processing.
Fields of use The composition according to the invention can be applied, in view of the foregoing, for disinfection, reduction in viable microbial count or improved hygiene, especially on a surface. In preferred embodiments, the composition is particularly suitable for application to the skin. For example, a surface such as the hands, face, body or oral cavity can be contacted properly with the composition of the invention. In other preferred embodiments, the surface is any hard surface. Typically, such hard surfaces are surfaces that commonly require cleaning and often also require sanitization or disinfection. Such surfaces can be found in many home or industrial environments, and may include, for example, kitchen surfaces and bathrooms, table tops, floors, walls, windows, utensils, cutlery and crockery. Such surfaces can be made from many different materials, for example, plastic, wood, metal, ceramic, glass, concrete, marble and painted surfaces. In other preferred embodiments, the compositions may be used for such disinfection, reduction in viable microbial counts or improved hygiene at sites other than the surfaces as described hereinbefore.
In preferred embodiments, the invention relates to compositions according to the invention for use as or incorporation into home care products and personal care products. More preferably, this embodiment of the invention relates to a composition according to the invention, which is a product for home care or a personal care product.
A "product for the care of the home" is a product for the treatment, cleaning, care or conditioning of the home or any of its contents. The foregoing includes, but is not limited to, compositions, products or combinations thereof, which refer to or have use or application in the treatment, cleaning, purification, care or conditioning of surfaces, furniture and home atmosphere and home contents. , such as clothes, fabrics and / or fabric fibers and the manufacture of all the above products. A "personal care product" is a product for the treatment, cleaning, care or conditioning of the person. The foregoing includes, but is not limited to, chemicals, compositions, products or combinations thereof which refer to or have use or application in the treatment, cleaning, purification or conditioning of the person (including in particular the skin, hair or oral cavity), and the manufacture of all the above. Household care products and personal care products are, for example, products marketed under mass trademarks, with non-limiting examples being soap bars, deodorants, shampoos and sanitizers / disinfectants of household surfaces.
Another preferred embodiment of the invention relates compositions according to the invention for use as or incorporation in industrial and / or institutional products. More preferably, this embodiment of the invention relates to a composition according to the invention, which is an industrial and / or institutional product. The industrial and institutional products are, for example, products being marketed under professional brands, non-limiting examples being industrial, institutional, janitorial and medical cleaning, cleaning-in-place, food services, veterinary and agricultural products. Industrial and / or institutional products also include products for cleaning the person (such as hand sanitizers) for medical offices, hospitals and / or other institutions.
In another preferred embodiment, the invention also relates to a method or use according to the invention that involves products for home care or personal care products. For example, the method according to the invention - which comprises the application of a composition according to the invention in step a - can be a method wherein that composition is a composition for use as or incorporation into home care products and personal care products as described herein. Similarly, in another preferred embodiment, the invention also relates to a method or use according to the invention that involves industrial and / or institutional products. For example, the method according to the invention - which comprises application of a composition according to the invention in step a - can be a method wherein said composition is a composition for use as or incorporation into industrial products and / or institutional as described earlier in this.
The products and / or methods for use in the field for home care or personal care are generally different from products and / or methods for use in the industrial and / or institutional field. Thus, for example, a product that is marketed as a product for home or personal care will not generally be marketed as a product for industrial and / or institutional use and vice versa. Therefore, certain embodiments of the present invention, when carried out, will relate to one field, but not to the other.
Examples The invention is illustrated by the following non-limiting examples.
Example 1: Evaluation of antimicrobial efficacy materials Monsubstituted phenols were purchased as chemicals fine from suppliers, such as Sigma Aldrich, Alfa Aesar and TCI Fine Chemicals.
A mixture of terpineol comprising approximately 88% by weight of (S) -alpha-terpineol and 12% by weight of gamma-terpineol was purchased from Sigma Aldrich and used throughout the examples (being referred to as alpha-terpineol or terpineol) unless otherwise specified.
General method for the evaluation of antimicrobial synergism The efficacies of antimicrobial agents can be compared in a useful way when determining the Minimum Biocidal Concentration (MBC). MBC is defined as the lowest absolute concentration of the particular asset that provides complete death (zero bacterial growth).
The different behaviors of inhibitory antimicrobials in isolation and mixtures have been extensively explored using the concept of Fractional Concentration and Fractional Inhibitory Concentration (FIC). See, for example, JRW Lambert and R Lambert, J. Appl. Microbiol 95, 734 (2003); T. Jadavji, CG Prober and R Cheung, Antimicrobial Agents and Chemotherapy (26), 91 (1984) and WO 2004/006876. These parameters can be defined as follows: FC (component a) = Concentration of component to tested in the mixture MIC (component tested as a simple asset) FIC (component a) = MIC (component tested in the mixture) MIC (component tested as a simple asset) By analogy, the Fractional Biocide Concentration (FBC) is given by: BCF (component a) = MBC (component tested in the mixture) MBC (component tested as a simple asset) The interactions between antimicrobials can be additive, synergistic or possibly antagonistic depending on whether the efficacy of the combination is equivalent to, greater than or less than that obtained for the same total concentration of the individual components when tested alone.
These relationships can be expressed mathematically by adding the fractional MBC values for all the components present in the mixture to give the "fractional biocidal index": ? FBC = BCF (component 1) + BCF (component 2) + BCF (component 3) + ··· etC so that ? BCF = 1 corresponds to additive or antagonistic bactericidal activity? BCF < 1 corresponds to synergistic bactericidal activity Experimental method The antimicrobial efficacy is tested against a representative pathogenic bacterial organism, Gram-negative Escherichia coli. The active concentrations are expressed in terms of the weight / volume percentage (% w / v) through Example 1.
Bacterial broth An overnight culture of Escherichia coli (strain 1 0536) was prepared in 50 ml of total volume of TSB broth, cultured for approximately 18 h at 37 ° C and stirred at 150 rpm. 1 ml of this E. coli culture overnight was transferred to 50 ml of fresh TSB broth and incubated at 37 ° C at 150 rpm for approximately 4 hours. This culture was separated in equal volumes and centrifuged at 4000 rpm for 15 minutes, washed with sterile saline (0.85% NaCl), centrifuged once more and resuspended in saline to give a final concentration of 0.8 O De2o equivalent to about 108. cells per milliliter for this particular organism. Here, OD6? O indicates the absorbance of a sample in a test piece with a path length of 1.0 cm at a wavelength of 620 nm. This bacterial broth was used to test against antimicrobial assets (in triplicate).
Protocol The following test describes the test of 8 materials using 6 dilutions through the middle of a 96-well microtiter plate (MTP). Using this approach it is possible to test 16 active (without replicates) with a complete dilution plate, replicating this layout in two halves of the plate columns, 1-6 and 7-12. 1M solutions of the test assets were prepared in dimethyl sulfoxide (DMSO). The stock solutions of the assets at 1.11 times the desired final concentration were prepared by diluting the DMSO solutions in water, so that, for example, a 0.89% w / v solution was prepared for a desired "in test" concentration. 0.8% w / v in order to allow further dilution of the active when the bacterial suspension is added (dilution of 270 μ? to 300 μ?), as described below.
The aliquots (270 μl) of the materials at 1.11 times the final concentration were dispensed into the MTP cavities along a column (A1-H1). This MTP was labeled as the "rating plate".
In another MTP, labeled as "Dilution plate", 270 μ? of neutralizing solution D / E of DIFCO Composition was added to column 1. The composition of the neutralizing solution was as follows: pancreatic digestion of casein, 5.0 g / l; Yeast extract, 2.5 g / l; Dextrose, 10 g / l, sodium thioglycolate, 1.0 g / l, sodium thiosulfate, 6.0 g / l; sodium bisulfite, 2.5 g / l; polysorbate 80, 5.0 g / l; lecithin 7.0 g / l; purple bromocresol, 0.02 g / l with a pH in the range 7.6 ± 0.2. 270 μ? of tryptone diluent solution was added to all remaining cavities of the dilution MTP (columns 2-6).
The bacterial broth (30 μ?) Was then added to the 270 μ? prepared from the active solution in the Classification plate and mixed, using a multichannel pipette with 8 tips for aspirate and dispense the same volume of bacterial broth in parallel to 8 cavities in rows A-H. After a contact time of 15 seconds, the mixtures were extinguished by transferring volumes of 30 μ? of the mixtures in the 270 μ? of neutralizing solution D / E in the prepared dilution plate, using suction to mix. After exactly 5 minutes in the neutralizing solution D / E, volumes of 30 μ? from column 1 to column 2 of the dilution MTP and were mixed, before additionally transferring volumes of 30 μ? from column 2 to column 3. This process was repeated by serially diluting the bacteria through the plate to the col um na 6.
Volumes of 30 μ? from each cavity in the dilution MTP were transferred onto pre-labeled segment of tryptone soy agar plates (TSA) starting from the lowest bacterial concentration (highest dilution, column 6) to the highest bacterial concentration. high (column 1). The TSA plates were allowed to rest for approximately 2 hours so that the 30 μ? They could be dried and the plates then inverted and incubated overnight at 37 ° C before enumerating the bacterial colonies at the labeled dilutions to determine the effects of the bacterial growth actives.
Calculation of results The average bacterial survival numbers N M BS (expressed in Log CFU / ml) are obtained by first determining the segment of the TSA plate, where the number of bacterial colonies is an accountant From the number of colonies in this segment, N MBS is calculated by the formula: N MBS = log. { NCOi 10DF 1 00/3} Here, Ncoi is the colon count, and DF is the dilution factor taken from the MTP cavity corresponding to the TSA plate segment (ie, DF can vary from for extinction, to 6 for the highest dilution) . The factor 1 00/3 is a conversion factor for the volume of the inoculum spot for one milliliter.
Each test test was performed in triplicate. The average bacterial survival results reported are the average of such triplet, the error is the corresponding standard deviation.
Thus, a NM BS value of approximately 7 corresponds to an account of approximately 3 colonies for the fifth dilution cavity, ie, with DF = 5. Such a content of approximately 7 is generally observed when bacteria are exposed to non-biocidal materials . In case no surviving colonies are observed in any segment of the TSA plate, this is interpreted as complete morbidity and a value of N MBS = 0 is reported.
Validation All test results were validated by running each test test in parallel with four control experiments in the same MTP. All control experiments are executed exactly according to the previous protocol, but with the following active ingredients: To 0.025% (w / v) thymol B 0.15% (w / v) alpha-terpineol C 0.025% (w / v) thymol + 0.15% (w / v) alpha-terpineol D without active component The control experiments A, B and D validate a test assay but do not show bacterial killing, whereas the control experiment C, comprising a synergistic combination of thymol and alpha-terpineol according to WO 201 0/046238 A1 validates an assay test when showing complete bacterial death.
A reference experiment according to the previous protocol, but without active component, showed that DMSO does not affect bacterial growth at the concentrations present in the test solutions in this protocol (< 5% (w / v)), as see in Table 4.
Table 4 Results The above method was applied to assess the antibacterial efficacy of the isopropyl methylphenols according to the invention. Table 5 shows the antibacterial activities of isopropyl-methylphenols, both alone and in conjunction with terpineol.
Table 5: Antibacterial activities of thymol and isopropyl-methylphenols alone and in combination with terpineol Example Concentration Concentration of NMBS S.D. phenol C (phenol) (% terpineol [log weight / volume) CTE P (% weight / volume) CFU / ml] 1: 1 '0.075% thymol 0 0 1: 2 * 0.05% thymol 1: 3 * 0.025% thymol > 7 0.1 1: 4 * 0.5% 1: 5 * 0.4% 1: 6 * 0.3% 0.2 1: 7 * 0.15% 0.2 1: 8 * 0.05% 3-isopropyl-5-methylphenol 1: 9 * 0.025% 3-isopropyl-5- 7.6 0.1 methylphenol Common examples The determination of the parameter? FBC, which is used as The mean of the synergistic antimicrobial action of compositions according to the present invention requires the determination of the Minimum Biocidal Concentrations (MBCs) of the relevant active ingredients first. As described above, MBC for an active can be defined as the lowest active concentration that provides zero bacterial survival in the particular medium. The data for the examples (1: 1 to (1: 3) show that the MBC value for thymol is 0.05% (w / v) For alpha-terpineol, the compositions (1: 4) to (1: 7), shows that the MBC is 0.4% w / v The same analysis has been performed for selected isopropyl-methylphenols and is summarized in Table 6 below These MBC values constitute the upper limits for the respective MBCs in the particular medium used in these examples Table 6: Minimum biocidal concentrations of antimicrobial components It is clear from the data in Table 6 that 3-ylpropyl-5-methylphenol and 4-isopropyl-3-methylphenol according to the present invention are antimicrobially effective.
Synergistic interactions The tested combinations of the selected sopropymethylphenols with terpineol provide complete bacterial killing in the examples (1: 10), (1: 1 1), (1: 14) - (1: 16). Using the MBC values listed in Table 6 above, the values of the fractional MBC for the components present in these mixtures and the experimental FBC of the compositions can be calculated in order to discriminate between combinations that provide evidence of synergistic effects, as opposes additive biocidal effects. The results of this analysis are given in Table 7.
Table 7: Degree of synergistic interactions between mixtures of binary compounds for compositions that provide complete bacterial death BCF of terpineol: Cterpineol / MBCterpineol ° Criterion for synergy: (? BCF < 1) For the Examples for which the value? FB C is below 1 in Table 7 provide evidence for synergistic interactions, according to the criteria set. Therefore, these examples show how the antimicrobial efficacy of terpineol and the isopropyl-methylphenols according to the invention are improved when applied together. Such synergies allow reduction in the concentrations of the antimicrobials required to achieve complete death. For example, 0.4% w / v of terpineol is required to achieve complete bacterial kill when tested in isolation, but this can be reduced 2.7 times to 0.1 5% (w / v) when used in combination with 0.025% w / v of 4-isopropyl-3-methylphenol or 0.025% w / v of 3-isopropyl-5-methylphenol.
Comparative examples Comparative examples (1: 17) and (1: 18) show that compositions comprising terpineol and phenolic compounds that are not compounds according to the present invention at concentrations comparable with those in the examples according to the invention do not result in fast antimicrobial action.
Example 2 In this Example, a wide range of chemical combinations was tested in the presence of high-resolution MBC assays of isopropyl-methylphenols in the presence of various concentrations of terpineol. The materials were from the same origin as for Example 1. The synergy tests were conducted using standard microtiter plate assays with phosphate buffer containing 35% dipropylene glycol (DPG). High resolution M BCs were determined by adding varying amounts of microbicide to a column of a microtiter plate and making subsequent ten-fold dilutions using an automated liquid handling system to obtain a series of endpoints ranging from 0.002% to 1 % of the test compound. The MBC plate was inoculated one column at a time with the test microorganism. An aliquot of the inoculated cavity was transferred within 15 seconds to a plate containing a neutralizing agent (D / E Neutralizing Broth), mixed and maintained for 5 minutes before being transferred to a growth plate containing trypticase soy broth ( TSB). The TSB plate was incubated at 37 ° C and read by the presence / absence of growth in 24 hours. The lowest level tested that provided complete death (as evidenced by the lack of growth on the microtiter plate) of the test organisms in 15 seconds is defined as the minimum biocidal concentration (MBC) throughout Example 2 .
The synergy of the combinations of the present invention was determined against the same bacteria as in Example 1, Escherichia. coli (E. coli, ATCC # 10536), at a concentration of approximately 1 x 1 08 bacteria per ml. This microorganism is representative of natural contaminants in many consumer and industrial applications. The plates were visually evaluated for microbial growth (turbidity) to determine the M BC after 24 hours of incubation time at 37 ° C.
The test results for synergy demonstration of the combinations of the present invention are shown below in Table 8. The table shows the specific combinations of two components; results against proven microorganism; the end-point activity in% by weight as measured by the M BC for the first component alone (3-acetyl-methyl-phenol, MB CA), for the second component alone (terpineol, M BCB), for the first component in the mixture (CA) and for the second component in the mixture (Ct >); the value? F BC calculated; and the range of synergistic proportions for each combination tested (First Component to Second Component or? /?) against the particular microorganism.
The data in the tables below include the range of proportions that were found synergistic. (Data that was collected outside the synergistic ranges are not reported). These data demonstrate that certain combinations of 3-isopropyl-5-methylphenol according to the present invention and terpineol show more enhanced control over microorganisms than would be expected if the combinations were additive rather than synergistic.
Table 8 First component (A) = 3-isopropyl-5-methylphenol Second component (B) = terpineol The proportions of (E) -2- (prop-1-enyl) phenol to terpineol tested ranged from 1/3025 to 1/400. The synergistic proportions of 3-isopropyl-5-methylphenol to terpineol ranged from 1/6/06 to 1/5.
The results of Examples 1 and 2 demonstrate that a synergistic antimicrobial effect of the isopropyl methylphenols according to the invention and terpineol is obtained over a wide range of concentrations and proportions.
Example 3 The antimicrobial efficacy of compositions according to the invention, comprising an isopropyl-methylphenol and terpineol were tested following the same protocol and using the same terpineol as described for Example 1. The results are presented in Table 9.
Table 9: Antibacterial activity of isopropylmethylphenols combination with gamma-terpineol against E. coli By analogous reasoning as described for Example 1, it follows from the comparative examples (3: 1) to (3: 4) that the MBC of gamma-terpineol under the given conditions is at least 0.3% w / v. Examples (3: 8) and (3: 1 1) demonstrate improved antimicrobial action of combinations of 4-isopropyl-3-methylphenol and gamma-terpineol.
Example 4: Automated evaluation of efficacy on the basis of surfactants Preparation of samples In these examples, the efficacy of combinations of isopropyl-methylphenols and terpineol were tested in a surfactant cleansing formulation comprising 2.85% sodium cocoyl glycinate and 1.85% sodium lauroamphoacetate. This corresponds to 50% dilution of use with water of a typical pure formulation containing 5.7% cocoyl glycinate and 3.7% sodium lauroanfoacetate during hand washing. The solutions were prepared so that the concentrations of the components of surfactants and test assets were 1.1 times the final desired concentration in order to allow dilution with the bacterial inoculum in the test. The solutions were manually adjusted to pH 1 0.0 by addition in the form of drops of sodium hydroxide solution, as measured with a pH meter at room temperature. The solutions of the isopropyl-methylphenols and / or terpineols were prepared up to 24 hours before the test. The same terpineol was used as in Example 1.
Test methodology The efficacy of the combinations of the present invention was determined against the same bacteria as in Example 1, Escherichia coli (E. coli-ATCC # 1 0536), at a concentration of approximately 1 x 1 08 bacteria per ml.
The tests were conducted using standard microtiter plate assays using an automated liquid handling system. 270 μ? of the surfactant test solution were pipetted into each well of the microtiter plate (untreated microtiter plates N unc F Gamma I rradiated 96F transparent polystyrene) and 30 μ? of the bacterial suspension were then added. After exactly 1 5 seconds of bacterial exposure, a volume of 30 μ? of bacterial cells was removed and transferred to 270 μ? of extinguishing solution D / E. After 5 minutes in the D / E extinction, the optical density (OD) was measured for each plate in turn at two specific wavelengths (450 nm and 590 nm). These provide a dual verification of antimicrobial activity, since the reading of O D450 is specific to the yellow color of the D / E extinction when the Bacterial growth is observed, whereas O D590 is specific for the initial purple color of the D / E extinction, which is retained if no bacterial growth is observed. After the zero time OD measurements, the plates were then incubated at 37 ° C overnight (16 hours) before repeating OD measurements. The delta OD values were calculated by subtracting OD values at 16 hours from the initial value at time zero from those at time = 16 hours. Bacterial growth is observed as an increase in O D450 and a decrease in O D690. To identify antibacterially effective systems (those that prevent appreciable bacterial growth after incubation), the following threshold changes in OD readings have been adopted: if (1), O D450 increases by less than 0.2 absorbance unit (AU) on incubation and (2). OD590 decreases by less than 0.35 AU over incubation. Conversely, where O D450 increases by more than 0.1 AU and O D590 decreases by more than 0.1 AU after incubation, corresponding to a color shift from purple to yellow, the test system allows bacterial growth and is not considered effective . Four replicate measurements have been made for each test system. The number of replica cavities that show either bacterial growth or no growth is also easily assessed by the eye following the color change. Thymol and terpineol were tested either alone or in combination for comparison purposes.
The dose responses for individual components and binary mixtures of assets at a fixed concentration ratio were generated by sequential dilution of liquors with additional surfactant solution to obtain a series of end points varying from 0.2 to 0.025% of isopropyl-methylphenol and 0.5% to 0.1% of terpineol. In each case, the binary mixtures were evaluated in the weight-to-weight ratio of isopropyl-methylphenol to terpineol of 1: 2.5.
Table 10: Antibacterial activities of isopropyl-methylphenols alone, and in combination with terpineol in model surfactant solution 4:28 0.2% 4-isopropyl-3- 0.5% 0.17 0.01 0.30 0.02 0 methylphenol 4: 29 * 0.125% 4-isopropyl-3- 0.3125% -0.45 0.01 0.58 0.01 4 methylphenol * Examples marked with an asterisk (*) are comparative examples (a) Concentration of isopropylmethylphenol as specified (b) Concentration of terpineol (c) DeltaOD (450 nm) = OD450 (time = 16 hours) - OD450 (time zero) (d) DeltaOD (590 nm) = OD590 (time = 16 hours) - OD590 (time zero) (e) Nrep = No. of replicas showing growth (out of 4) (f) S.D. = standard deviation Table 1 1: Minimum biocidal concentrations of antimicrobial components in 2.85% sodium cocoyl glycinate + 1.85% sodium lauroamphoacetate solution at pH 10 Results The surfactants used are not themselves antimicrobially active against E. coli at the concentrations employed as shown by the results of Ex. (4: 1) in Table 10. In this way, any antimicrobial efficacy can be attributed to isopropyl-methylphenols and / or terpineol. Table 11 presents the MBC values determined in a similar manner as described for Example 1. The isopropyl methylphenols tested have a higher MBC than the highest concentrations tested, in the presence of the specified surfactants.
The results of Table 10 show that 3-isopropyl-5-methylphenol and 4-isopropyl-3-methylphenol show bactericidal efficacy of 15 seconds (complete death in all 4 replicates) against E. coli when tested in combination with alpha-terpineol at concentrations lower than its MBC in the same surfactant formulation (comprising cocoyl glycinate and lauroanfoacetate).
In this way, it was found that the isopropyl methylphenols according to the invention and in particular 3-isopropyl-5-methylphenol and 4-isopropyl-3-methylphenol show improved antimicrobial action in combination with terpineol in the presence of surfactant, in particular cocoyl glycinate and lauroanfoacetate.

Claims (10)

REIVI N DICACIONES 1 . An antimicrobial composition comprising:
1. 0.001 to 5% by weight of one or more isopropyl-methylphenols, i. 0.001 to 5% by weight of terpineol, and ii i. a carrier; wherein the one or more isopropyl methylphenols are selected from 3-isopropyl-5-methylphenol and 4-isopropyl-3-methylphenol; and where terpineol is selected from the group consisting of alpha-terpineol, beta-terpineol, gamma-terpineol, delta-terpineol, 4-terpineol and mixtures thereof.
2. An antimicrobial composition according to claim 1, comprising i. 0.05 to 0.4% by weight of one or more isopropyl-methylphenols, and i. 0.05 to 1% by weight of the terpi neol.
3. An antimicrobial composition according to claim 1 or 2, comprising from 1 to 80% by weight of one or more surfactants.
4. An antimicrobial composition according to claim 3, wherein the one or more surfactants are anionic, nonionic or a combination of anionic and nonionic surfactants.
5. An antimicrobial composition according to claim 3 or 4, wherein the one or more surfactants are selected from the group consisting of soaps, alkylsulfates and linear alkyl benzene sulphonates.
6. A solid antimicrobial composition according to any of claims 3 to 5, comprising: to. 0.05 to 5% by weight of one or more isopropyl-methylphenols, b. 0.05 to 5% by weight of terpineol, c. 5 to 30% by weight of water, and d. 30 to 80% by weight of the surfactants.
7. A method for disinfecting a surface comprising the steps of to. applying a composition according to any of claims 1 to 6 on the surface; Y b. Remove the composition from the surface.
8. A method according to claim 7, wherein the disinfection time T of said method is less than 300 seconds, preferably less than 60 seconds, more preferably less than 15 seconds; where T is defined as the time elapsed from the moment of adding the composition to a microbial culture until the number of microbes per unit volume of the culture is reduced by a factor of 1 00 000; and wherein the initial number of microbes preferably exceeds approximately 100,000,000 microbes per milliliter and wherein the composition is preferably a liquid composition.
9. The use of a composition according to any of claims 1 to 6 for improved hand hygiene.
10. The use of a composition according to any of the claims 1 to 6 for improved oral hygiene. SUMMARY The present invention relates to an antimicrobial composition and to a method for disinfection that involves the antimicrobial composition. It refers in particular to an antimicrobial composition for applications of personal cleansing, oral care or cleaning of hard surfaces. It was found that compositions comprising one or more isopropyl methylphenols, terpineol and a carrier provide synergistic antimicrobial action. In a preferred aspect, the composition also comprises 1 to 80% by weight of one or more surfactants.
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